Clinical Analysis of Kasabach-Merritt Syndrome in 17 Neonates

Vera

Prof. H. Hendro S. Yuwono, dr. Ph.D. SpB-(K)V

Background

• Kasabach-Merritt syndrome (KMS), also known as giant hemangioma with thrombocytopenia (characteristics)

• Incidence: about 1 % of cases of hemangioma, 80% present within 1 year after birth, mortality rate ranges from 10 to 37%.

• May result in life threatening multi-organ hemorrhage.• This study evaluated the clinical characteristics,

treatments, and outcomes in neonates with KMS, in order to find out the optimal therapy.

Methods

• Period: January 2007-2012• Sample: 17 patients with giant hemangioma who were

eventually diagnosed with KMS and treated with steroid therapy, arterial embolization, and vincristine, depending on their individual responses to treatment.

• Location: Guangzhou Women and Children’s Medical Center, China.

• The diagnostic criteria for KMS were as follows:

(1)Hemangioma of the skin or internal organs;

(2)Thrombocytopenia and consumptive coagulopathy;

(3)Hemangioma confirmed by B-mode ultrasonography, color Doppler flow imaging, computed tomography (CT), or magnetic resonance imaging (MRI);

(4)Other causes for the abnormalities excluded, such as hypersplenism or idiopathic thrombocytopenic purpura.

Results

The patients were 13 males and 4 females, aged 17 hours to 28 days at admission. 4 had visceral hemangiomas and 13 cutaneous hemangiomas. All had thrombocytopenia and coagulation disorders. Intravenous steroid therapy was initially effective in 6 patients (of which 3 relapsed) and ineffective in 11. The 11 patients with a poor response to steroids and the 3 who relapsed underwent arterial embolization therapy, which was effective in 9 patients (of which 1 relapsed), ineffective in 4, and discontinued before completion in 1. Subsequently, 4 patients in whom arterial embolization therapy was ineffective and 1 with relapse were treated with vincristine. This was effective in 4 patients, and the other died of disseminated intravascular coagulation.

3 relapsed6 effective

11 ineffective

Steroid

Arterial Embolization

4 ineffective 9 effective 1 discontinued

1 relapsedVincristine

1 died4 effective

Discussion

• KMS should be considered in children with unexplained thrombocytopenia and coagulation disorders.

• Routine blood testing showed varying degrees of low hemoglobin concentration, low plasma fibrinogen level, and prolonged prothrombin time.

• B-mode Ultrasonography, CT, and MRI showed the size, appearance, and layers of hemangiomas, distinguished hemangiomas from vascular malformations.

• There are currently no consensus guidelines for the treatment of KMS.

• Comprehensive sequential therapy including steroid therapy, interferon, arterial embolization, vincristine, radiotherapy, and surgery.

• In infants, glucocorticoid therapy is considered to be a good choice for initial drug treatment, because it can inhibit fibrinolysis and thrombosis, stimulate hematopoiesis in the bone marrow to increase release of platelets into the bloodstream, decrease the level of anti-platelet anti- bodies, and increase platelet count (only effective in 30% to 50% of patients).

(A) The patient with multiple cutaneous hemangiomas (more than 20 hemangiomas of different sizes) and multiple hepatic hemangiomas. (B) The patient with cutaneous hemangiomas on back and axilla. (C) The patient with cutaneous hemangiomas on left leg. (D) The patient with cutaneous hemangiomas on right knee.

• In this study, patients were treated with intravenous dexamethasone 1 mg/kg/day as first-line treatment, 6 patients responded well and the platelet count started to increase after 3–8 days. In 3 patients, the platelet counts remained normal for the following year. The hemangiomas did not enlarge or bleed, and regressed within 1–2 years. In the other 3 patients, the platelet counts subsequently decreased and underwent arterial embolization. No relapses were observed over the following year.

• Steroid therapy was effective in 35.3% of patients, but the relapse rate was high (50%), resulting in effectiveness rate of only 17.6%.

• Arterial embolization has been used to treat vascular tumors for many years and is useful for controlling symptoms and promoting regression of hemangiomas. In this study, the remaining 11 patients and the 3 who relapsed underwent arterial embolization with a mixture of bleomycin A5 (8–12 mg/m2), iodinated oil (2 mL), and dexamethasone (2 mg). 1 patient discontinued therapy because of the severity of disease and financial difficulty.

• Arterial embolization was effective in 64.3% of patients (effective in 9 patients). The platelet counts increased at 2–5 days and reached normal levels at 10–16 days. Only 1 patient developed recurrence at 5 months and underwent repeat embolization and vincristine chemotherapy (1 mg/m2 weekly).

• Vincristine, actinomycin, and cyclophosphamide can induce tumor regression and normalization of coagulation parameters.

• As for the remaining 4 patients, the platelet count decreased at 1 week after surgery and treated with vincristine chemotherapy 1 mg/m2 weekly, resulting in improvement. 3 of these patients did not relapse during a year of follow-up, and the other patient died of severe disseminated intravascular coagulation.

• Vincristine was effective in 80% of these patients. No adverse effects related to chemotherapy were observed.

• Local injection of urea has been used to successfully treat hemangiomas and vascular malformations, and may be useful for the treatment of neonatal KMS.

• Interferon therapy can be considered as a second-line drug treatment that is effective in 50% to 60% of patients, but it only has weak inhibitory effects on endothelial cell and vascular growth, and continuous treatment is needed.

• The safety and effectiveness of radiotherapy for the treatment of KMS should be evaluated in further clinical studies with follow-up over a few decades.

Conclusion

• Neonatal KMS has a high relapse rate after steroid therapy. Arterial embolization has a good rate of effectiveness. Combined steroid therapy and arterial embolization can be used as first-line treatment for neonatal KMS. If this combination is ineffective, vincristine therapy may be useful.

Reference

• Wang P, Zhou W, Tao L, Zhao N, Chen XW. Clinical Analysis of Kasabach-Merritt Syndrome in 17 Neonates. BioMed Central Pediatrics. 2014; 14: 146.

THANK YOU